This application claims benefit to foreign application IT TO99A000693 filed in Italy on Aug. 5, 1999.
The present invention relates to angioplasty stents. In particular, this invention relates to a stent structure that minimizes restenosis.
The term xe2x80x9cstentxe2x80x9d is used to indicate in a general way those devices intended for intravascular application (for example inside a blood vessel), usually carried out by catheterization followed by in-situ expansion in order to exert an action of local support to the lumen.
For a general overview of vascular stents the reader may usefully refer to the work xe2x80x9cTextbook of Interventional Cardiologyxe2x80x9d, ed. Eric J. Topol, W.B. Saunders Company, 1994, and in particular section IV of vol. II entitled xe2x80x9cCoronary Stentingxe2x80x9d.
The subject has also attracted a large number of patent documents, as witness, for example, EP-A-0 806 190, EP-A-0 850 604, EP-A-0 847 766, EP-A-0 857 470, EP-A-0 875 215, EP-A-0 895 759, EP-A-0 895 760.
The clinical use of these devices, which in recent years has grown considerably in popularity, must address the need to ensure an effective impediment to the phenomenon usually known as restenosis. This is a phenomenon (linked to the manifestation of physiological mechanisms that, furthermore, are not yet clearly understood) whereby the stenosis site, after having been reopened by the implant of the stent, gradually tends to close up again, usually owing to gradual tissue growth.
Various solutions have been proposed for dealing with this problem: they essentially involve a local action designed to impede the phenomena that give rise to the restenosis. In particular, a number of solutions have been investigated in which drugs are released locally or radioactive sources are used locally.
These solutions, especially those based on the localized and controlled release of drugs, have themselves to address the problem of how this localization is to be effectively carried out at the stent implant site. In the case of agents designed to be released by the stent, it is important to ensure that the majority of the agents are released gradually into the walls of the vessel rather than being washed away relatively rapidly by the flow of blood passing through the lumen of the stent. This is particularly important because clinical experiments show that the mechanisms of reaction of the vessel subjected to the stent implant occur at the level of a reaction by the vessel wall within a period of time typically ranging from 1 to 6 months from implantation.
It is an object of the present invention to provide a solution capable of improving on previously attempted solutions, from a number of points of view. First, it is wished to be able to achieve a reliable connection, or anchoring, of therapeutic agents to the stent, and in particular a connection that will not be influenced either by the movement of the stent as it dilates, which is characteristic of the implanting operation, or by possible surface treatments (such as deposition of a surface layer of biocompatible carbon-containing material) which may have been applied to the stent.
Second, it is wished to be able to produce a collection of components capable of acting in effect as a xe2x80x9creleasing machinexe2x80x9d that will deliver a controlled release of restenosis-impeding agents, particularly as regards the possibility of precisely controlling the release kinetics, with the further possibility of selectively controlling, in time or in relation to other parameters, the release of diverse agents.
Again, it is wished that the functions specified above be able to be carried out without negative impacts on the other characteristic aspects of the functionality of the stent, e.g., by ensuring that, whether at the time of implantation or later, the lumen of the stent does not become a site for obstructions to the free flow of blood.
In one aspect, this invention is stent structure having a longitudinal axis and having a substantially tubular body capable of being dilated from a radially-contracted position to a radially-expanded position comprising a stent having an inner surface and an outer surface; and at least one fiber disposed adjacent one of the surfaces of the stent, the fiber adapted to provide a therapeutic agent. Preferably, the therapeutic agent is an agent that impedes restenosis. The fibers preferably are attached to the stent structure such that the fibers do not substantially retard dilation of the stent structure from the radially contracted position to the radially expanded position. The therapeutic agent may be contained within a nucleus embedded in the at least one fiber or may be within a lumen defined by the at least one fiber. The therapeutic agent may be in a nucleus where the nucleus is in a particle contained within an outer envelope. Preferably, the outer envelope is bioerodible. The particle may range in size from 100 to 200 nanometers. Preferably, the fiber is bioerodible.
The stent structure may also comprise a sheath interposed between the stent and the fiber. The sheath may be a biocompatible material, such as silicone, and may be permeable. Alternatively, the sheath may comprise a metallic material or a polymeric material and have an apertured structure such as a mesh, so that it may expand when the stent structure expands. The sheath may be coated with a layer of a biocompatible carbon-containing material. The fiber may be anchored to the sheath. There may be multiple fibers disposed around the stent. The fiber preferably is extensible in the direction of the longitudinal axis. The fiber may be wound around the stent structure in a helical path with a winding pitch of 45xc2x0 or 60xc2x0 relative to the longitudinal axis. The fiber may comprise a porous structure. The fiber diameter can range between about 30 and 100 micrometers and have wall thickness ranging between about 10 and 20 micrometers. The therapeutic agent may comprise one or more drugs selected from anti-inflammatory and antimitotic agents.
In a second embodiment, this invention is a kit for impeding restenosis in vasculature comprising a stent that can be dilated from a radially contracted position to a radially expanded position; at least one fiber comprising a restenosis-impeding agent; a catheter adapted to deliver the stent and the at least one fiber to a site of restenosis; and a container configured to house the stent, the at least one fiber, and the catheter. The fiber may comprise a sheet configured to be wound around the stent or a tubular sock configured to be fitted onto the stent.
In a third aspect, this invention is a component for delivering a therapeutic agent that impedes restenosis, the component for use in combination with a stent having a longitudinal axis and having an inner surface and an outer surface, the component comprising at least one fiber configured to be placed adjacent a surface of the stent; a particle contained by the at least one fiber, and a nucleus contained within the particle, the nucleus adapted to contain the therapeutic agent. The particle may be contained within a lumen defined by the at least one fiber and/or may comprise the nucleus contained within an outer envelope. The therapeutic agent that impedes restenosis may further comprise one or more drugs selected from anti-inflammatory and antimitotic agents.
In a fourth aspect, this invention is a method of impeding restenosis in a patient""s vasculature comprising: providing a stent having an inner surface and an outer surface and a longitudinal axis and being capable of being dilated from a radially-contracted position to a radially-expanded position; providing at least one fiber adapted to deliver a restenosis impeding agent; providing a delivery catheter; mounting the stent and the at least one fiber onto the delivery catheter; and advancing the delivery catheter to the patient""s vasculature to deliver the stent and the at least one fiber at the site of stenosis.